We are continuing our analysis of the site of action of maytansine in cells and the source of the high specificity for tumor versus normal cells. We are using two different cells lines, CHO cells and KB nasocarcinoma cells, which show a 15 fold difference of sensitivity to the drug. We are investigating three possibilities. One is that the amount of tubulin is different in the two different types of cells since we have shown that maytansine binds avidly to tubulin. A second, is that the differences are a function of transport rates. A third is that the cells have different amounts of some maytansine binding protein which is not directly related to mitotic function. We are guessing that ligandins may be such proteins because of some of the properties of maytansine. Cells with high amounts of such binding proteins should be less sensitive to maytansine since they should have less free drug. In addition, we are starting to select temperature sensitive resistant cells as one mode of comparing cells with the same genetic background but which show different sensitivities to the same drug at two different temperatures.